Investigating the Differential Distribution and Kinesin-Mediated Transport of Calcium Channels in Neurons

Investigating the differential distribution and kinesin-mediated transport of calcium channels in neurons Voltage-gated calcium channels (CaV channels) play a key role for normal neuronal function by providing Ca2+ entry at particular sites on the surface of the cell soma, axons and dendrites. Disruption in the spatial distribution of these channels likely causes change of neuron transmission that may lead to neurological disorders. Thus, CaV channels have to be properly transported and targeted to the correct neuronal subcellular domains. However, very little is known about the trafficking mechanisms of CaV channels in neurons. We and other groups have previously shown that many neuronal ion channels are transported by kinesin motors suggesting the potential participation of kinesins in transporting CaV channels. In this proposal, we will 1) study the subcellular distribution patterns of neuronal CaV channels, 2) examine whether they are transported via microtubule tracks by specific kinesins, and 3) further characterize the transport machinery with regard to the axonal targeting of CaV2 channels. Completion of this project will not only expand our knowledge on the axonal targeting mechanism of the typical presynaptic CaV2 channels in details, but also provide a basic overview of microtubule-based transport processes for other CaV channels that allows for further in-depth characterization. Furthemore, examining the mechanisms underlying localization of CaV channels will establish a foundation for understanding the general processes involved in the subcellular targeting of membrane proteins. In the long term, the information we obtain would be valuable for understanding the pathophysiology of neurological disorders that result from trafficking abnormalities of ion channel proteins.

Project ID:PA9801-1802
External Project ID:NSC97-2311-B182-004-MY3